There are currently four sodium-glucose co-transporter-2 (SGLT-2) inhibitors that have a licence for use within the UK: canagliflozin, dapagliflozin, empagliflozin and ertugliflozin.
Licences for medications in the UK are issued by the Medicines and Healthcare products Regulatory Agency (MHRA). A product licence will set out the criteria for which a medication has been approved for use and is granted based on review of clinical trial efficacy and safety data. The pharmaceutical company responsible for the manufacture of the medication will produce a document called the Summary of Product Characteristics (SmPC) outlining the properties, conditions for use and licensing information of the product.
The term ‘off-label’ describes the use of a medication outside of the criteria defined within the licence. The term ‘unlicensed’ refers to the use of a medication that has not had a licence granted for use by the MHRA in the UK.
SGLT-2 inhibitors are prescription-only medicines (POM). The UK licences for the SGLT-2 inhibitors were initially focused on glycaemic effectiveness, however they are continually updated in response to any new data published on the individual medications. For example, the empagliflozin (Jardiance) licence was updated in 2017 after the cardiovascular benefit data from the EMPA-REG OUTCOME trial were published (1).
These data resulted in a subsequent amendment to the wording of the therapeutic indication, removing ‘glycaemic control’ as the only treatment goal of empagliflozin therapy. In June 2020, canagliflozin also underwent a licence update expanding its indications based on trial data from CREDENCE (2).
In late 2020, dapagliflozin had a new therapeutic indication added to the licence as a consequence of the DAPA-HF trial to include the treatment of symptomatic chronic heart failure with reduced ejection fraction (HFrEF), closely followed by empagliflozin in July 2021 also adding HFrEF as a licensed indication after review of the EMPEROR-REDUCED data (3, 4).
In August 2021, an additional update to the dapagliflozin licence based on review of the results from the DAPA-CKD study gave dapagliflozin an indication to be used for the treatment of chronic kidney disease (CKD) (5).
The most recent updates to the SGLT-2 inhibitor licensed indications have expanded the heart failure licences of empagliflozin and dapagliflozin to preserved ejection fraction after the addition of EMPEROR-PRESERVED and DELIVER studies to the evidence base (6, 7).
Upon publication of the EMPA-KIDNEY Trial in November 2022 (8), a licence update for empagliflozin to include the treatment of CKD is expected.
An additional medication to consider is sotagliflozin; a combination SGLT-1/SGLT-2 inhibitor. Sotagliflozin, is not licensed or currently available in the UK. It was initially approved for use in the EU by the European Medicines Agency, for people with type 1 diabetes mellitus (DM) with a BMI of ≥27 kg/m2, where optimal insulin therapy has failed to adequately maintain glycaemic control – this approval has now been withdrawn (9). The National Institute for Health and Care Excellence (NICE) pre-emptively published a technology appraisal (NICE TA622) recommending the use of sotagliflozin with the same indication as the EMA criteria above, pending any UK licensing (10). A summary for the use of the different SGLT-2 inhibitors in relation to CKD stage can be found in Table 4.1, below:
Table 4.1 Dosing of SGLT-2 Inhibitors based on current UK regulatory licences (all doses are once daily)
